The major macromolecular constituents of most connective tissues are collagen and the class of polyanionic molecules known as proteoglycans. Lysozyme is a polycationic protein also found in such tissues, and whose function therein is unknown. The extracellular matrix of cartilage is an accessible tissue from which at least two of these molecular species are readily extractable. Since the integrity of the connective tissue matrix is probably a function of the relation these classes of molecules bear to each other, the current study will focus on the structural and functional interaction of these substances. The particular problems to be investigated include the stoichiometry of complex formation between lysozyme and proteoglycans, identification of the sites within the molecule where lysozyme-proteoglycan and proteoglycan-collagen complexes form, evaluation of the possible role served by lysozyme in formation of proteoglycan aggregates, study of the effect of lysozyme and/or proteoglycans on collagenase activity, comparison of collagen interactions with proteoglycan subunits and proteoglycan aggregates, and indirect analysis of interactions between connective tissue components by study of the residual composition tissues in which one or more of the major constituents has been altered.